1. Field of the Invention
The present invention relates to an anhydride derivative, and more particularly, to a anhydride derivative of 2-(S)-(6-methoxy-2-naphtyl)-propanoic acid, a preparation method and a use thereof.
2. Description of Related Art
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as 2-(S)-(6-methoxy-2-naphtyl)-propanoic acid (Naproxen) are anti-inflammatory agents, analgesics and fever reducers, and thus play an important role in treating diseases. However, due to the gastrointestinal side effects, NSAIDs are not used for long term treatments. WO95/09831 discloses nitric esters of NSAIDs including 2-(S)-(6-methoxy-2-naphtyl)-propanoic acid 4-nitrooxybutyl ester (Naproxcinod), which has anti-inflammation and pain-relieving activities, is of good tolerance, and also reduces the gastrointestinal side effects. Naproxcinod (also named as NO-naproxen, AZD-3582, HCT-3012C or nitronaproxen) is a cyclooxygenase-inhibiting nitric oxide donator (CINOD), which reduces the gastrointestinal side effects resulting from Naproxen and lowers blood pressure via nitric oxide (NO) release.
WO95/09831 discloses the preparation of Naproxcinod, by the reaction of the sodium salt of Naproxen and halo-butanol, or the reaction of the sodium salt of Naproxen and 1,4-dihalobutane and the nitration with silver nitrate, so as to obtain Naproxcinod. WO98/25918 and WO2001/010814 disclose the preparation of Naproxcinod by using acyl halides of Naproxen. WO2004/020384 discloses the preparation of Naproxcinod by using salts of Naproxen. WO03/045896 discloses the preparation of Naproxcinod from the reaction of a sulfonate ester and Naproxen, halides or salts thereof. WO2009/149053 discloses the preparation of Naproxcinod from the reaction of 1,4-dihalobutane and Naproxen, halides or salts thereof. However, the acyl halides of Naproxen are not chemically stable, and easily racemized. Further, the above-mentioned conventional methods are complicated in steps, the temperature control and the long duration, and the yield is only 70% to 80%. Moreover, the products in the conventional method need to be further purified for obtaining high purity of Naproxcinod. In addition, the cost of the conventional methods is high due to the usage of silver nitrate or chromatography.
Hence, there is a need to provide a preparation method for obtaining Naproxcinod with high purity and high yield.